NR AOSS
AU Freitas,A.R.O.; Coitinho,A.S.; Roesler,R.; Walz,R.; Minetti,A.; Choi,H.; Zanata,S.M.; Izquierdo,I.; Brentani,R.R.; Martins,V.R.
TI Cellular Prion Interaction With Laminin Mediates Memory Formation Through PKA and p44/42MAPK
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-02
PT Konferenz-Poster
AB The physiological functions of the cellular prion protein (PrPc) are under intensive investigation. PrPc is a high affinity receptor for a peptide at the carboxi-terminal domain of the laminin (LN) gamma-1 chain leading to neuronal differentiation and maintenance. Given the exquisite abundance of PrPc and LN in the hippocampus, we decided to investigate whether the PrPc-LN interaction might play a role in memory formation. We blocked these proteins in normal rats by intra-hippocampal infusions of specific antagonist antibodies and measure short (STM) and long-term memory (LTM) formation for an aversively motivated learning task. This approach is particularly relevant as the use of any constitutively knockout animal, particularly in behavioral tests, has been receiving a lot of criticism since both compensatory mechanisms and the genetic background may influence the results. Our data show that anti-PrPc and anti-LN antibodies impaired both STM and LTM. The effects of both antibodies were consistent with the blocking of cAMP-dependent Protein Kinase A (PKA) and p44/42 Mitogen-activated Protein Kinase (MAPK) activity at 0 hour post-training and PKA at both 0 and 2 hours post-training. In addiction, the inhibitory effects of anti-PrPc antibodies both in memory formation and in PKA/p44/42MAPK activities are abolished by co-administration of the per se inactive LN gamma-1 chain carboxy-terminal peptide. Therefore, our data indicate that the PrPc -LN interaction plays a pivotal role in memory formation through activation of classical signaling pathways.
AD Adriana R.O. Freitas, Alexandra Minetti, Humberto Choi, Silvio M. Zanata, Ricardo R. Brentani, Vilma R. Martins, Ludwig Institute for Cancer Research, São Paulo, SP, Brazil; Adriana S. Coitinho, Rafael Roesler, Ivan Izquierdo, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Roger Walz, CIREP, HC-Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto ,SP, Brazil
SP englisch
PO Deutschland